1. Field of the Invention
The present invention relates to an apparatus and method for facilitating temperature controlled dermal drug delivery. Specifically, the present invention relates to a configuration and use of an integrated temperature control device and a dermal drug delivery system. More specifically, the present invention relates to the configuration and use of an integrated layer of transdermally delivered drug formulation and a controlled heat aided drug delivery patch (hereinafter CHADD patch). The transdermally delivered drug formulation provides a non-invasive method for delivery of a therapeutic agent. The CHADD patch provides temperature control and facilitates dermal drug absorption. The present invention provides the convenience of an integrated dermal drug formulation and a CHADD patch while maintaining the stability of the CHADD patch and the drug formulation.
2. Relevant Technology
The dermal administration of pharmaceutically active compounds involves the direct application of pharmaceutically active formulations to the skin, wherein the skin absorbs a portion of the pharmaceutically active compound which is then taken up by the skin, tissues under the skin and the bloodstream. Such administration has long been known in the practice of medicine and continues to be an important technique in the delivery of pharmaceutically active compounds. For example, U.S. Pat. No. 4,286,592 issued Sep. 1, 1981, to Chandra Sicaran shows a bandage for administering drugs to a user""s skin consisting of an impermeable backing layer, a drug reservoir layer composed of a drug and a carrier, and a contact adhesive layer by which the bandage is affixed to the skin.
For some drugs such dermal administration offers many important advantages over other delivery techniques, such as injection, oral tablets, and capsules. These advantages include being non-invasive, avoiding first pass metabolism of the drug in the liver when the drug is taken orally and absorbed through the gastrointestinal tract, and in some instances, avoiding undesired high peaks and low valleys of concentration of pharmaceutically active compounds in the patient""s bloodstream. Other possible advantages include: avoidance of a harsh environment in the stomach, reduced total dosage, reduced cost in some instances, and improved compliance with prescribed use.
The term xe2x80x9cdermal drug delivery systemxe2x80x9d or xe2x80x9cDDDSxe2x80x9d, as used herein, is defined as an article, apparatus, or method for administering pharmaceutically active compound(s) for delivery into the skin, the regional tissues under the skin, the systemic circulation, or other targeting site(s) in a human body via skin permeation. The term xe2x80x9cDDDSxe2x80x9d in this application, unless otherwise specified, only refers to those systems in which the main driving force for drug permeation is the drug concentration gradient (passive permeant).
The term xe2x80x9cskin,xe2x80x9d as used herein, is defined to include stratum corneum covered skin and mucosal membranes.
The term xe2x80x9cdrug,xe2x80x9d as used herein, is defined to include any pharmaceutically active compound, including but not limited to, compounds that treat diseases, injuries, undesirable symptoms, and improve or maintain health.
In DDDSs, a drug(s) is usually contained in a formulation, such as a hydro-alcohol gel, and may include a rate limiting membrane between the formulation and skin for minimizing the variation in the permeation of the drug. When a DDDS is applied to skin, the drug begins to transport out of the formulation, and transport across the rate limiting membrane (if present). The drug then enters the skin, enters blood vessels and tissues under the skin, and is taken into the systemic circulation of the body by the blood. At least some DDDSs have certain amounts of pharmaceutically active compound in or on the skin side of the rate limiting membrane (if present) prior to use. In those DDDSs, that portion of the drug on the skin side of the rate limiting membrane will enter the skin without passing through the rate limiting membrane. For many drugs, a significant portion of the dermally absorbed drug is stored in the skin and/or tissues under the skin (hereinafter referred as xe2x80x9cdepot sitesxe2x80x9d) before being gradually taken into the systemic circulation (hereinafter referred to as xe2x80x9cdepot effectxe2x80x9d). This depot effect is believed to be at least partially responsible for the delayed appearance of the drug in the systemic circulation after the application of some DDDSs and for continued delivery of the drug into the systemic circulation after the removal of some DDDSs from the skin.
After placing a DDDS on the skin, the drug concentration in the targeted tissue or blood typically remains at or near zero for a period of time, before starting to gradually increase and reach a concentration deemed to be medicinally beneficial, called the xe2x80x9ctherapeutic levelxe2x80x9d (the time it takes to reach the therapeutic level is referred to hereinafter as the xe2x80x9conset timexe2x80x9d). Ideally, the concentration of the drug in the targeted tissue or blood should plateau (i.e., reach a substantially steady state) at a level slightly higher than the therapeutic level and should remain there for extended period of time. For a given person and a given DDDS, the xe2x80x9cconcentration of the drug in the targeted tissue or bloodstream vs. timexe2x80x9d relationship usually cannot be altered under normal application conditions.
The onset time and the delivery rate of the drug into the targeted area(s) of the body for a typical DDDS are usually determined by several factors, including: the rate of release of the drug from the formulation, the permeability of the drug across the rate limiting membrane (if a rate limiting membrane is utilized), the permeability of the drug across the skin (especially the stratum corneum layer), drug storage in and release from the depot sites, the permeability of the walls of the blood vessels, and the circulation of blood and other body fluid in the tissues (including the skin) under and around the DDDS. Although these primary factors affecting onset time and delivery rate are known, no existing DDDS is designed to have alterable delivery rate in the course of the application of the drug and therefore no existing DDDS is able to provide for example, an increased concentration of a pharmaceutically active compound in a patient""s bloodstream for a short period of time (a narrow peak) in the course of the application of a DDDS, when it is desirable to do so.
While a DDDS works well in many aspects, current dermal drug delivery technology has some serious limitations, including: 1) the onset time is undesirably long for many DDDSs; 2) the rate that the drug is taken into the systemic circulation or the targeted area(s) of the body cannot be easily varied once the DDDS is applied onto the skin and, when the steady state delivery rate is achieved, it cannot be easily changed; and 3) the skin permeability is so low that many drugs are excluded from dermal delivery because the amount of drug delivered is not high enough to reach a therapeutic level. In addition, temperature variations in the skin and the DDDS are believed to contribute to the variation of dermal absorption of drugs.
It is known that elevated temperature can increase the absorption of drugs through the skin. U.S. Pat. No. 4,898,592 issued Feb. 6, 1990 to Latzke et al., relates to a device for the application of heated transdermally absorbable active substances which includes a carrier impregnated with a transdermally absorbable active substance and a support. The support is a laminate made up of one or more polymeric layers and optionally includes a heat conductive element. This heat conductive element is used for distribution of the patient""s body heat such that absorption of the active substance is enhanced. U.S. Pat. No. 4,230,105, issued Oct. 28, 1980 to Harwood, discloses a bandage with a drug and a heat-generating substance, preferably intermixed, to enhance the rate of absorption of the drug by a user""s skin. Separate drug and heat-generating substance layers are also disclosed. U.S. Pat. No. 4,685,911, issued Aug. 11, 1987 to Konno et al., discloses a skin patch including a drug component, and an optional heating element for melting the drug-containing formulation if body temperature is inadequate to do so.
While it is known that elevated temperatures can increase the absorption of a drug through the skin, the use of a separate heating element in the administration of dermal drug delivery systems to increase the absorption of drugs through the skin may present a number of disadvantages (when compared with a dermal drug delivery system having an integrated temperature control component). For example, the use of a separate temperature control element can complicate the administration of the therapeutic agent by requiring the patient or care giver to take additional steps to employ the temperature control element, such as acquiring, storing and preparing the separate temperature control element and the administrating and removing the separate temperature control element.
Also, as the complexity of administrating the therapeutic agent increases, the likelihood of compliance by the patient or caregiver with the prescribed use of the temperature control element tend to decrease, potentially reducing the effectiveness of the prescribed treatment. If the prescribed use requires a patient to purchase, store, prepare, administer and then remove a separate heating element in addition to administering a DDDS, the patient may feel inconvenienced by the additional time and choose to forego the prescribed use of the separate temperature control element. Furthermore, the use of a separate temperature control element is limited by the compatibility between a given temperature control element and the DDDS with which the temperature control element is to be used. The shape, formulation and configuration of the DDDS may prevent effective use of a separate heating element, where the separate heating element is not specifically designed for use with the DDDS.
While there are disadvantages to the use of a separate temperature control element with a DDDS, combining the two without careful consideration may be difficult and problematic. For example, one could attempt to combine the temperature control element with a DDDS by making the drug formulation in the DDDS capable of generating heat when exposed to oxygen or by another mechanism. However, in order to do so it would be necessary for the heat generating medium and the drug formulation to be completely compatible with each other. When using an exothermic oxidation reaction to generate heat, if the heat generating medium comprising iron powder, activated carbon and water is mixed with an aqueous gel-based local anesthetic formulation, it cannot generate heat properly because, among other reasons, the gel in the local anesthetic formulation would prevent oxygen from entering the heat generating medium.
Another approach which initially appears straightforward would be simply affixing a CHADD patch onto a drug patch, and placing the integrated patch into an air-tight container. This approach was utilized by Albert Argaud in U.S. Pat. No. 4,963,360. The Argaud patent teaches the use of a base sheet to which is applied on one side a gelatin layer holding the medication, and on the other side a composition designed to have a exothermic reaction when exposed to air. Because there is no heat regulating mechanism in the Argaud patent, the absorption of the medicinal component will not be controlled. Uncontrolled absorption can cause serious reactions in patients due to drug overdose and under dose. These attendant side affects out weigh the benefits provided by the exothermic reaction. In addition, to the problems of regulating the heat in these early DDDS""s, other problems such as the lack of any insolation or any engineering to direct the heat into the body also reduce the effectiveness and consistency of the exothermic reaction.
Since these early patches also did not provide for a mechanism for sealing the medicinal layer against the skin, rapid evaporation of the medicinal component can occur once the gel is exposed to air. Moreover, without a means to affix the patch securely to the skin, there is no assurance of proper absorption. As can be seen by looking at the example provided by the Argaud reference, there is a limited contact area between the medicinal layer and the contact area is likely to vary, affecting the amount of drug absorbed. Another problem with the Argaud patch is that because of the packaging of the device, the air within the package is allowed to communicate with both the drug formulation and heat generating medium. This approach allows the exchange or transfer of substance(s) between the heat generating medium and the drug formulation during storage, which may compromise either or both the drug formulation and the heat generating medium. For instance, if the heat generating medium has a proper ratio of iron powder, activated carbon, salt, wood powder and water and the drug formulation is in the form of a hydrogel, the heat generating medium may absorb water vapor from the drug formulation, and thus change the desired concentrations of water in both the heat generating medium and the drug formulation. This problem as it applies to the use of fentanyl is explained in greater detail below.
The difficulty of combining a temperature control unit with a DDDS is illustrated by the following example of combining a CHADD oxidation patch with a fentanyl DDDS. By affixing a heating component having a heat generating medium as described in the paragraph above disposed to a fentanyl patch having a formulation containing alcohol and water (similar to the formulation in Duragesic patches), one could attempt to form an integrated patch, and this integrated patch could be sealed in an air-tight container. Although the air-tight container would separate the integrated patch from the outside environment, and although a barrier film may be placed between the CHADD heating component and the drug formulation, the alcohol and water in the fentanyl formulation could still migrate into the space in the air-tight container is the form of vapors and be absorbed into the heat generating medium. The activated carbon in the heat generating medium has a strong tendency to absorb volatile substances. Therefore over time, the fentanyl formulation would lose a significant amount of alcohol and water.
Both alcohol and water play very important roles in the transdermal delivery of fentanyl. At least one function of alcohol in the formulation is to increase skin permeability, so that the desired amount of fentanyl can be absorbed. Water and alcohol also serve as the solvent of fentanyl in the formulation. If a temperature control apparatus and a fentanyl DDDS are combined as explained in the paragraph above, significant amounts of alcohol and water would be lost during storage and skin permeability would not be increased as designed, leading to lower dermal absorption of fentanyl. In addition, fentanyl solubility and concentration in the formulation would be changed, which would change the driving force for transdermal fentanyl permeation. As a result, fentanyl absorption from the transdermal patch would likely be quite different from the designed rates and be quite unpredictable. This could cause serious drug under dose or overdose.
Furthermore, if enough alcohol and water are absorbed into the heat generating medium, the function of the heating component may also be compromised. In a heat generating medium using activated carbon, the activated carbon has a tendency to absorb moisture from the surrounding environment. If the water quantity in the heat generating medium is increased too much, the heat generating medium will not generate heat properly. Thus it is important to shield the heat generating medium from moisture. It is similarly important to protect the heat generating medium from exposure to oxygen to prevent the oxidation reaction from transpiring prematurely.
Thus, it is very important to have good separation between the drug formulation and the heating component in an integrated patch, even if the integrated patch is sealed in an air-tight container. This separation should not only prevent direct transfer of substance(s) between the drug formulation and the heating component (i.e., permeation) but also prevents the transfer or exchange through vapor via the space in the airtight container. It would therefore be an advancement in the art to provide a configuration that combines the convenience and ease of use of an integrated temperature control component with a dermal drug delivery component that can simultaneously prevent undesired transfer of substance(s) between the temperature control component and dermal drug delivery system, shields them as necessary from ambient oxygen and undesired solvents, and prevents undesired gain or loss of the solvent to the environment.
In view of the foregoing, it is an object of some of the embodiments of the present invention to provide a dermal drug delivery system (DDDS) which integrates a temperature control component with a dermal drug delivery component, thereby allowing for reduced complexity and redundancy in manufacturing, distributing and storing of the system, while preventing transfer of substance(s) among the components and the outside environment.
It is another object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component, thereby allowing the integrated components to be stored in one container, while preventing transfer of substance(s) among the components and the outside environment.
It is yet another object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component, thereby allowing for greater convenience of use than the use of a separate temperature control element and dermal drug delivery system while preventing transfer of substance(s) among the components and the outside environment.
It is still another object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component, thereby promoting patient compliance with prescribed use, while preventing transfer of substance(s) among the components and the outside environment.
It is further an object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component that conveniently combines the components and prevents oxygen and ambient air from flowing into the heat generated medium during storage.
It is yet another object some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component that conveniently combines the components and prevents absorption of moisture in ambient air into the temperature control component or into the drug delivery component while in storage.
It is a still further object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component that conveniently combines the components and prevents absorption of the ingredients into the drug formulation and into the temperature control component while in storage.
It is yet another object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component that conveniently combines the components and limits undesired interaction between the components while in storage.
It is also an object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component that conveniently combines the components and maintains a proper ratio of ingredients in a temperature control component and in a drug delivery component while in storage.
It is another object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug delivery component that conveniently combines the components and prevents significant modification of the components while in storage.
It is another object of some embodiments of the present invention to provide a DDDS which integrates a temperature control component with a dermal drug formulation applicator thereby facilitating the application of therapeutic agents which are not practically stored in combination with the temperature control component.
The present invention integrates a drug delivery component, such as a transdermal drug delivery system, with a temperature control component, such as a CHADD patch. The drug delivery component comprises a drug formulation applicator and a drug formulation secured to the drug formulation applicator. A barrier and/or compartment prevents undesired substance(s) transfer between the temperature control component and the drug delivery component. A barrier and/or compartment also prevents exchange transfer or absorption of volatile substances between the drug delivery and temperature control components and the external environment. The temperature control component comprises a temperature modification element and a temperature control which can control or adjust the heat generated by the temperature modification element.
The drug delivery component may be similar to known dermal drug delivery systems having a drug disposed within a formulation, the formulation adhering to or contained within a drug applicator. A drug formulation applicator can be any structure or process in a dermal drug delivery system which facilitates or results in the delivery of the drug or drug formulation to the skin of a patient, for example, a gauze pad secured to adhesive tape. The drug applicator may include a rate limiting membrane between the drug formulation and the user""s skin, or alternatively the formulation may be in direct contact with the skin. A physical barrier, such as an impermeable medical packaging film, provides means for preventing exchange or substance(s) between the drug delivery component and the temperature control component via direct permeation or vapor absorption. The drug applicator with the drug formulation are secured to the means for preventing exchange. This drug delivery component is integrated with the temperature control component to form the integrated patch. Additionally, a layer of medical adhesive tape may be secured to the barrier film or other part of the integrated patch, thereby providing means for attaching the integrated patch to the skin of the patient.
The absorption of the therapeutic drug is usually determined by a number of factors including: the diffusion coefficient of drug molecules in the drug formulation, the permeability coefficient of the drug across a rate limiting membrane (if any), the concentration of dissolved drug in the formulation, the skin permeability to the drug, the body fluid (including blood) circulation in the skin and/or other tissue under the skin, permeability of the walls of capillary blood vessels in the sub-skin tissues and absorption into and release from depot sites in the sub-skin tissues. It is believed that controlled heating can potentially affect each one of the above factors, and thus, it is desirable to have a temperature control component integrated with a drug delivery component.
The integrated patch of the present invention provides for the use of a wide variety of drug formulations. The formulation itself may take various forms such as liquid, gel, cream, paste, or solid. Generally, a therapeutic agent is mixed or dissolved into the drug formulation. The drug delivery system of the present invention contemplates the use of a transdermally administered drug in a drug formulation including, but not limited to, drugs such as analgesics, androgens, anesthetics, and anesthetic agents. The drug formulation applicator is configured to hold the drug formulation such that the drug formulation on the applicator can be easily removed from its storage pocket and administered to a patient""s skin.
The temperature control component has a temperature modification element which may be a heat generating element (for example, a CHADD patch) and a temperature control, to allow the user to adjust the temperature. CHADD patches are specifically designed to improve the efficiency and therapeutic effectiveness of dermal drug delivery systems. An important feature of the CHADD patch is that it can quickly increase skin temperature to a temperature around 39xc2x0 C.-43xc2x0 C. The CHADD patch can maintain skin temperature in that range for an extended period of time. This not only provides consistent heating, but also prevents skin damage which could be caused by over heating when using other heating methods.
One embodiment of the CHADD patch comprises a shallow chamber defined by a bottom, a frame wall, and a cover. Within the shallow chamber is a heat generating medium which, upon contact with ambient oxygen, can generate heat. The chamber has a cover which is made of a material impermeable to oxygen. The cover has areas which are open to allow oxygen into the chamber. The openings maybe selectively covered, partially covered, or opened by the user to control air flow into the chamber and the heat generated therein. Alternatively, certain or all areas of the cover may be covered by a membrane with certain permeability to air. Thus the cover can allow ambient air to flow into the chamber at a desired rate, which in turn causes the oxidation reaction in the heat generating medium to generate a desired temperature on the skin. The bottom of the chamber and frame wall are also substantially impermeable to oxygen. Within the chamber the heat generating medium which generally comprises activated carbon, iron powder, salt, and water. Agents that improve air flow, such as fine wood powder may also be added. The ratio of components in this embodiment is very important in order for the heat generating medium to work properly. For example, a typical ratio of approximately 5:16:3:2:6 of activated carbon:iron powder:fine wood powder:sodium chloride: and water (all weights) makes a reasonably good heat generating medium.
The CHADD patch which uses an oxidation reaction to generate heat needs to be stored in an air-tight container. When the patch is removed from the container, oxygen in the ambient air flows into the shallow chamber, initiating a heat generating oxidation reaction in the heat generating medium. The amount of heat generated per unit of time is controlled by the rate of the oxygen flow into the heat generating medium through the cover. Less than the entire number and size of holes on the cover can be utilized to further control the amount of heat generated per unit of time.
Effectively, combining a CHADD patch as a temperature control component with a dermal drug delivery component such as briefly described above, results in an integrated dermal drug delivery system patch (hereinafter xe2x80x9cintegrated CHADD patchxe2x80x9d).
The integrated CHADD patch design allows a person or care giver to more conveniently apply controlled heat for the purpose of more effective transdermal drug delivery. Additionally, the integrated CHADD patch design helps to prevent the misuse or improper use of controlled heat with transdermal drug delivery. The integrated patch provides for a more uniform heating of the associated drug formulation. When a patient uses a drug delivery system with a separate temperature control element, it is possible that improper placement of the temperature control element by the user or unintended displacement of the heating element may result in uneven heating of the drug formulation. A separate temperature control element requires the patient or care giver to determine which kind of element to use, when to initiate heating, when to terminate heating, what temperature range is appropriate, and where and how to direct or attach the heat from the separate temperature control element. The actual handling may vary from patient to patient and treatment to treatment. A patient or care giver could easily make the wrong decision concerning the issues listed above and thus misapply the separate heating element. Improper use of the temperature control element may yield improper drug dosage. The integrated heat component and drug delivery component help to reduce or eliminate the potential for misuse of a separate temperature control element.
A preferred embodiment of the integrated CHADD dermal drug delivery patch comprises a tray made of a material that is a good barrier to volatile liquid, especially water, and alcohol but not necessarily a good barrier to oxygen. The tray defines a shallow reservoir capable of accommodating both a drug formulation and drug formulation applicator. The drug formulation adheres to the drug formulation applicator. The drug formulation applicator is secured to a film which is a good barrier to volatile liquids. The film can be heat sealed to the edge of the tray to form a closed compartment defined by the reservoir within the tray and the film. The drug formulation resides within the compartment. Since both the tray and lid to the compartment act as barriers to solvents, when the compartment is sealed tight, it prevents the transfer of substance(s) between the drug formulation and the outside environment.
On top of the film is an adhesive tape that has an area slightly larger than the film. The adhesive side of the adhesive tape faces the film and the edges of the tape extend out beyond the edges of the film. The portion of the adhesive tape which extend beyond the edges of the film is used to secure the integrated patch to the skin of the user. The CHADD patch is secured on top of the adhesive tape, and is centered on the adhesive tape. It is desirable that the inside area of the CHADD patch containing the heat generating medium be substantially the same or slightly larger than the area of the drug formulation applicator, to provide for effective heating. In other words, when the CHADD patch is secured to the film barrier and drug applicator, the heat generating element should be present directly above any areas of drug formulation so that substantially all of the drug formulation (which is also the barrier film) is evenly and uniformly heated.
In the preferred embodiment, the outer-most edges of the lidding film are not sealed onto the tray, and an adhesive tape is placed on top of the lidding film with the adhesive side adhered to the lidding film. The size of the adhesive tape may be similar to that of the lidding film, or preferably, slightly larger than the lidding film. If the adhesive tape is slightly larger than the lidding film, the portion of the adhesive tape that extends beyond the edges of the lidding film is rested on the tray. When a patient is removing the tape from the tray for use, the adhesive tape can be peeled from the tray at one end. The portion of the lidding film that is not sealed onto the tray (but is adhered to the adhesive tape) comes up with the adhesive tape. As the peeling continues, the entire lidding film, and the drug formulation attached to it, comes up with the adhesive tape. The adhesive tape, with the CHADD patch on the upper side and the drug formulation in the lower side, is then used to affix the integrated patch onto the skin. The tray may be indented at the end(s) to facilitate the start of the peeling.
The integrated patch is sealed in an air-tight container. The formulation is completely sealed in the space between the tray and the barrier film, so no exchange of substances between the formulation and the heat generating medium or the outside environment may take place. The heat generating medium is further sealed by the air-tight container so it is completely contained in the space inside the air-tight container. Thus the drug formulation is completely isolated from both the temperature control component and the outside environment. The temperature control component is isolated from the drug formulation. When the integrated patch is sealed into an air-tight container, the temperature control component is also isolated from the outside environment. Thus, the CHADD patch can be integrated with the drug delivery component and can be stored together in an air tight compartment such as a pouch made of film which is a good barrier to both air and moisture.
In one embodiment of the integrated DDDS patch, the barrier for preventing undesired substance transfer between the drug delivery system component and the temperature control component may comprise one or more chambers or compartments in which the drug delivery component and temperature control component are isolated while remaining structurally integrated. The chambers may be impermeable substances as required by the specific drug formulation and temperature control component. Similarly, means for preventing transfer of substances between the drug delivery and temperature control components with the external environment may comprise a chamber or pouch in which the integrated CHADD patch is stored. The chamber or pouch may be impermeable to moisture, oxygen, light or other environmental factors as necessary.
In one embodiment of the integrated CHADD patch, means for preventing undesired heat loss is provided. Means for preventing undesired heat loss includes insulating materials used in the drug delivery and temperature control components. Other means for preventing undesired heat loss include using adhesives and other means for securing and sealing the integrated DDDS patch to the skin of the user so that heat does not escape through unsecured edges or corners of the drug delivery component and temperature control component, as well as customized shaping or molding of the integrated CHADD patch to more appropriately fit a specific part of the user""s body.
In one embodiment of the present invention, a means for preventing undesired heat loss is provided. In some instances it can be difficult to secure a corner of a patch to a user""s skin. FIG. 4 shows an integrated CHADD patch having a substantially oval shape. The oval shape does not have corners, as would a rectangular or square shaped patch. Thus the oval shape facilitates the prevention of heat loss through unsecured corners by eliminating corners which may be difficult to secure and result in undesired heat loss.
Another embodiment of the present invention provides a foam cover for the heat generating component. The foam tape cover has insulative properties which help to minimize heat loss through the cover and which help to prevent varying ambient temperatures from adversely affecting the heat generated by the CHADD component. Moreover, an insulative cover capable of insulating the exposed surfaces of the integrated CHADD patch is also contemplated.
It is often necessary for the heat generating medium and the drug formulation to be entirely sealed from each other and from the external environment during storage and/or use. It is also desirable to provide convenient application and use of both components despite the sophisticated sealing necessary to preserve the drug formulation and heat generating medium. The novel configurations in this invention provide both satisfactory separation of the components during storage and/or use, and convenience in application and use.
The temperature control component and the drug delivery component of the present invention are preferably isolated. The isolated drug delivery component and the isolated temperature control component are disposed to prevent or avoid undesired interaction with the environment and with other components of the device. For example, the isolated temperature control component can be an exothermic medium enclosed in a substantial air-tight environment having a barrier which prevents undesired substance transfer among the heat generating medium in the temperature control component, the environment and the drug delivery component. Similarly, the isolated drug delivery component may be enclosed in a substantially air-tight compartment and may have a barrier to prevent any undesired substance transfer or exchange among the outside environment, the temperature control component and the drug delivery component. Isolation requirements for each component may differ depending upon the heat generating medium and the drug formulation being used.
Without careful designing, attempts to combine heat produced by exothermic oxidation reactions and transdermal drug delivery may result in an inoperative or ineffective combination. Some are rendered inoperative or ineffective because the components are not properly and conveniently isolated. Substances from the drug formulation may be lost to and/or foul the heat generating oxidation reaction elements through vapor absorption. During storage, the loss of substance(s) from the drug formulation may cause the drug formulation to function significantly differently than originally desired. Furthermore, substance(s) from the temperature control component may undesirably interact with the drug formulation rendering it less effective or ineffective. Other combinations are difficult or impractical to produce and use.